[Xiaohe Granule improves breast hyperplasia in rats by promoting mammary epithelial cell apoptosis via activating the ASK1/MKK4/JNK signaling pathway].

Authors

Yu Zhang, Kang Sun, Juda Liu, Shuhan Wang, Jing Pei

Published in

Nan fang yi ke da xue xue bao = Journal of Southern Medical University. Volume 46. Issue 8. Pages 1936-1946. Aug 20, 2026.

Abstract

To explore the mechanism of Xiaohe Granule (XHG) for alleviating mammary hyperplasia in rats.
A non-pregnant female SD rat model of mammary hyperplasia was established by intramuscular injections of estradiol benzoate (0.5 mg/kg) and progesterone (5 mg/kg). With untreated rats as the control group, the rat models were treated with saline (model group) or low-, medium- or high-dose XHG daily gavage, or with high-dose XHG plus oral administration of GS-444217. After the treatments, nipple height, diameter, and uterine index of the rats were measured, and histological changes in the mammary tissue were observed with HE staining. The expressions of Ki-67 and caspase-3 protein in the mammary tissue were detected using immunohistochemistry, and mammary epithelial cell apoptosis was examined using TUNEL staining. Serum levels of E2, P, PRL, FSH, IL-1β, and TNF-α were detected using ELISA, and the expressions of ASK1/MKK4/JNK and apoptosis-related proteins were analyzed using RT-qPCR and Western blotting.
Compared with the normal control rats, the rats in the model group showed significantly increased mammary diameter, nipple height, and uterine index with obvious acinar hyperplasia, ductal dilation, and inflammatory cell infiltration in the mammary tissue. The rat models also showed significantly increased Ki-67 expression and serum levels of E2, P, PRL, FSH, IL-1β and TNF-α, markedly increased Bcl-2 expression, and lowered protein levels of p-ASK1/ASK1, p-MKK4/MKK4, p-JNK/JNK, caspase-3, and Bax in the mammary tissue. Treatment with XHG significantly reversed these changes in a dose-dependent manner. Treatment with GS-444217 significantly attenuated the ameliorative effect of high-dose XHG on mammary hyperplasia in the rat models.
XHG alleviates mammary hyperplasia in rats by promoting apoptosis of hyperplastic mammary epithelial cells via activating the ASK1/MKK4/JNK signaling pathway.

PMID:
42576502
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.

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